This is a resubmission of 1 K07 CA112529-01 "Hormones, hormone-related genes, and colorectal cancer." Candidate: Jennifer Hsiang-Ling Lin received her Ph.D. in 1997 at the University of Missouri-Columbia. She subsequently worked as a biostatistician in the Division of Biostatistics, Washington University in St. Louis between 1997 and 1999, and later began her research work in the field of statistical genetics in the Psychiatry Department at Washington University in St. Louis between 1999 and 2002. She is currently an Instructor in Medicine at Harvard Medical School (HMS). She is applying for this Career Development Award to acquire the methodological and theoretical research skills needed to become an independent scientist in cancer genetics and epidemiology. Sponsor and Environment: l-Min Lee, MBBS, ScD, is an Associate Professor of Medicine at HMS and co-investigator of the Women's Health Study (WHS). Nancy R. Cook, ScD, is an Associate Professor of Medicine (Biostatistics) at HMS and also co-investigator of the WHS. They have extensive experience training investigators in the fields of lifestyle and chronic diseases as well as numerous publications in these areas. Research: The proposed study will examine the associations between exogenous hormone use, reproductive factors, estrogen-synthesizing genes, estrogen and progesterone receptors, and colorectal cancer (CRC) risk in a large cohort of women from the WHS, a randomized clinical trial of vitamin E and low-dose aspirin in the primary prevention of cancer and cardiovascular disease among 39,876 women. As of 2007, an estimated 413 CRC cases will have occurred in the overall WHS cohort (288 with blood specimens). This proposed study will provide detailed assessment of the long-term effects of postmenopausal hormone therapy on CRC risk according to duration, formulation, and dosage in the WHS female cohort. In addition, the study will investigate duration of oral contraceptives use, parity, and cumulative exposure to endogenous estrogen (estimated from duration between menarche and menopause) in relation to CRC risk. Finally, the study will comprehensively examine the associations between putative functional polymorphisms and haplotype distributions of a set of common polymorphisms in the 17beta-hydroxysteroid dehydrogenase type 2 gene (HSD17B2), the aromatase cytochrome P450 gene (CYP19A1), estrogen receptor alpha (ESR1), estrogen receptor beta (ESR2), progesterone receptor (PGR) and CRC risk. Findings from the proposed study of estrogen and progesterone will enhance our understanding of these lifestyle and genetic factors in relation to colorectal carcinogenesis.